1. Field of the Invention
The present invention relates generally to the fields of medical oncology and the pharmacotherapy of human cancers. More specifically, the present invention relates to novel methods of treating cisplatin resistant or cisplatin non-resistant cancers using a combination of tamoxifen and cisplatin.
2. Description of the Related Art
The treatment of cancer patients with platinum coordination complex antineoplastic agents, such as cis-diamminedichloroplatinum (II) (cisplatin) has increased substantially in the last decade. Cisplatin is a antineoplastic agent that has proved useful in the treatment of multiple malignancies including testicular cancer, ovarian cancer, and small cell lung cancer. The mechanism of action is currently unknown but may be related to the ability of cisplatin to bind to DNA and form various types of inter- and intrastrand crosslinks that possibly interfere with both DNA and RNA synthesis.
Cancer patients eventually become resistant to treatment with platinum coordination complexes, such as cisplatin. If the patient dies of metastatic cancer, the cells of the metastatic foci are usually also characterized by their extreme resistance to single or combinations of the available chemotherapeutic drugs. In general, drug resistant tumors can be classified as temporary or permanent. The mechanism of resistance to cisplatin is unclear but may be related to decreased drug accumulation, elevation of intracellular concentrations of metallothioneines or glutathione which bind and inactivate cisplatin, or to decreased cisplatin-DNA adduct formation or repair.
Tamoxifen is an antiestrogen agent that has been used extensively in the treatment of women with breast cancer. The accepted mechanism of action of tamoxifen in breast cancer is via antagonism of the estrogen receptor leading to interference with estrogen induced cell growth.
One of the major problems in cancer therapy today is the ability of tumor cells to develop resistance to chemotherapeutic agents. This is particularly frustrating because a patient initially responds to the antineoplastic drug, such as cisplatin.
The prior art remains deficient in the absence of an efficient and efficacious method of preventing resistance or overcoming established resistance to platinum coordination complex anti-neoplastic agents. In addition, the prior art is deficient in the lack of an effective method of potentiating the cytotoxic effects of platinum coordination complex anti-neoplastic agents.